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Aldehyde dehydrogenase (ALDH) inhibitors and activators target enzymes that oxidize aldehydes to carboxylic acids. The human ALDH superfamily uses NAD+ as cofactor and includes cytosolic ALDH1A1 and mitochondrial ALDH2. ALDH2 removes acetaldehyde and lipid peroxidation products such as 4-hydroxynonenal. In 2008 the small-molecule activator Alda-1 increased ALDH2 activity and reduced ischemic damage in rat hearts. High ALDH1 activity was reported in 2007 as a marker of normal and malignant human mammary stem cells. NCT-501, NCT-505 and NCT-506 inhibit ALDH1A1 and are used in cancer stem cell studies. RV01 targets ALDH2, while dyclonine hydrochloride and the herbicide propachlor also inhibit ALDH isoforms.
ALDH2 activator 1 is an allosteric agonist of aldehyde dehydrogenase 2 (ALDH2). This compound enhances cardiac function and mitigates myocardial necrosis in murine models of myocardial ischemia-reperfusion. It holds potential for advancing research in cardiovascular diseases, particularly in the context of myocardial infarction.
